Blast and blunt injuries to the eye can cause a series of mechanical disruptions to the ocular contents including: commotio retinae, traumatic cataract, disruption of the zonular attachments to the lens, angle recession, iris dialysis, and rupture of the pupillary sphincter. Treatment of these injuries has been limited to mechanical repair (when possible) of the iris, replacement of the crystalline lens with plastic lens implants, and repair of retinal detachments. There has been no treatment to repair the cellular architecture of the retina or the anterior chamber. Amnion-derived Cellular Cytokine Solution (ACCS), a novel multi-factorial solution of cytokines, growth factors, lipids, micro-RNAs, amino acids and vitamins, made from cultured Amnion-derived Multipotent Progenitor (AMP) cells, has been shown to foster limited regeneration of brain tissue architecture after injury (Z. Chen, F. C. Tortella, J. R. Dave, V. S. Marshall, D. L. Clarke, G. Sing, F. Du, X.-C. M. Lu, Human amnion-derived multipotent progenitor cell treatment alleviates traumatic brain injury-induced axonal degeneration, J. Neurotrauma 26, 1987-97 (2009); Ying Deng-Bryant, PhD, Zhiyong Chen, PhD, Christopher van der Merwe, BS, Zhilin Liao, MS, Jitendra R. Dave, PhD, Randall Rupp, PhD, Deborah A. Shear, PhD, and Frank C. Tortella, PhD, Long-term administration of amnion-derived cellular cytokine suspension promotes functional recovery in a model of penetrating ballistic-like brain injury, J. Trauma Acute Care Surg 73(2) Supplement 1, 156-164, 2012), all of which are incorporated herein by reference in their entirety. It also contains many of the proteins found in tears including mucins and Tissue Inhibitors of Metalloproteinases-1 and 2 (TIMP-1 and TIMP-2). ACCS is anti-inflammatory and is favorable to cellular regeneration which may unlock the keys to regeneration of traumatized eye tissues previously thought to be irreparable. In addition, ACCS is anti-inflammatory and anti-apoptotic for certain neuronal cells (Z. Chen, F. C. Tortella, J. R. Dave, V. S. Marshall, D. L. Clarke, G. Sing, F. Du, X.-C. M. Lu, Human amnion-derived multipotent progenitor cell treatment alleviates traumatic brain injury-induced axonal degeneration, J. Neurotrauma 26, 1987-97, 2009). Apoptosis has been implicated as a primary cause of photoreceptor cell death as a result of retinal detachment (Murakami, Y., Notomi, S., Hisatomi, T., Nakazawa, T., Ishibashi, T., Miller J., and Vavvas, D. Photoreceptor cell death and rescue in retinal detachment and degenerations., Progress in Retinal and Eye Res., 37, 114-140, 2013), incorporated herein by reference in its entirety.
Traumatic optic neuropathy and optic nerve avulsion are among the six leading types of ocular injury that required specialized ophthalmic care during Operation Iraqi Freedom (Cho and Savitsky, “Ocular Trauma Chapter 7”, in Combat Casualty Care: Lessons learned from Oef and Oif, by Brian Eastbridge and Eric Savitsky, pp. 299-342, Ft. Detrick, Md.: Borden Institute (US) Government Printing Office, 2012), incorporated herein by reference in its entirety. Sixty percent of traumatic head injuries result in neuro-ophthalmic abnormalities (Van Stavern, et al., “Neuro-Ophthalmic Manifestations of Head Trauma”, J Neuro-Ophthamol 21(2):112-117, 2001) (incorporated herein by reference in its entirety) half of which involve the optic nerves or visual pathways. Traumatic injury to neurons results in axonal damage and irreversible neuronal loss resulting in permanent deficits. While a number of potential neuroprotective therapies have been identified in animals, these single agents have universally failed to translate to therapies in human clinical trials (Turner, et al., “The science of cerebral ischemia and the quest for neuroprotection: navigating past failure to future success”, J Neurosurg 118(5):1072-1085, 2013, incorporated herein by reference in its entirety). Combination therapies that affect several cellular targets are likely needed to prevent neuronal damage.
Delivery of a drug to the optic nerve is clearly difficult. Proteins can be delivered non-invasively via the intranasal route to the optic nerve and the central nervous system (CNS) (Ross, et al., “Intranasal administration delivers peptoids to the rat central nervous system”, Neuroscience Letters 439:30-33, 2008; Zuo, et al., “SIRT1 promotes RGC survival and delays loss of function following optic nerve crush”, Invest Ophthalmol Vis Sci 54(7):5097-5102, 2013), incorporated herein by reference in their entirety. Intranasal insulin has been successfully delivered to the CNS in clinical trials for the treatment of Alzheimer's disease (Craft, et al., “Intranasal insulin therapy for Alzheimer Disease and amnestic mild cognitive impairment”, Arch Neurol 69(1):29-38, 2012), incorporated herein by reference in its entirety.